Details of the Drug Combination

General Information of Drug Combination (ID: DC0CLGE)

Drug Combination Name

Indazole derivative 5 Pralatrexate

Indication

Disease Entry	Status	REF
High grade ovarian serous adenocarcinoma	Investigative	[1]

Component Drugs

Indazole derivative 5 DMM1I8R

Pralatrexate DMAO80I

Small molecular drug

2D MOL

3D MOL

High-throughput Screening Result

Testing Cell Line: OVCAR-4

Zero Interaction Potency (ZIP) Score: 0.27

Bliss Independence Score: 2.67

Loewe Additivity Score: 2.3

LHighest Single Agent (HSA) Score: 1.64

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)

Indazole derivative 5 Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
ABL T315I mutant (ABL T315I)	TTZJTWA	ABL1_HUMAN	Inhibitor	[4]
Fusion protein Bcr-Abl T315I mutant (Bcr-Abl T315I)	TTIV39N	BCR_HUMAN-ABL1_HUMAN	Inhibitor	[4]
------------------------------------------------------------------------------------

Indication(s) of Pralatrexate

Disease Entry	ICD 11	Status	REF
Breast cancer	2C60-2C65	Approved	[2]
Peripheral T-cell lymphoma	2A90.C	Approved	[2]
Primary cutaneous peripheral T-cell lymphoma not otherwise specified	N.A.	Approved	[3]

Pralatrexate Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Polypeptide deformylase (PDF)	TT9SL3Q	DEFM_HUMAN	Inhibitor	[5]
------------------------------------------------------------------------------------

Pralatrexate Interacts with 2 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Folate transporter 1 (SLC19A1)	DTOSN46	S19A1_HUMAN	Substrate	[6]
Proton-coupled folate transporter (SLC46A1)	DTDJEMI	PCFT_HUMAN	Substrate	[6]
------------------------------------------------------------------------------------

Pralatrexate Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Folylpolyglutamate synthase (FPGS)	DECWT2V	FOLC_HUMAN	Metabolism	[7]
------------------------------------------------------------------------------------

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Adult T acute lymphoblastic leukemia	DCDX1HD	MOLT-4	Investigative	[8]
Childhood T acute lymphoblastic leukemia	DC6NUZ6	CCRF-CEM	Investigative	[8]
Clear cell renal cell carcinoma	DCFL9OB	TK-10	Investigative	[8]
Adenocarcinoma	DCEYO90	HCT-15	Investigative	[1]
Adenocarcinoma	DCRLRPD	HCC-2998	Investigative	[1]
Lung adenocarcinoma	DCPTMXH	HOP-62	Investigative	[1]
Minimally invasive lung adenocarcinoma	DC9TAXZ	NCI-H322M	Investigative	[1]
------------------------------------------------------------------------------------


⏷ Show the Full List of 7 DrugCom(s)

References

1	Loss of function mutations in VARS encoding cytoplasmic valyl-tRNA synthetase cause microcephaly, seizures, and progressive cerebral atrophy.Hum Genet. 2018 Apr;137(4):293-303. doi: 10.1007/s00439-018-1882-3. Epub 2018 Apr 24.
2	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6840).
3	Pralatrexate FDA Label
4	Bcr-Abl tyrosine kinase inhibitors: a patent review.Expert Opin Ther Pat. 2015 Apr;25(4):397-412.
5	Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
6	Antifolates in cancer therapy: structure, activity and mechanisms of drug resistance. Drug Resist Updat. 2012 Aug;15(4):183-210.
7	Pralatrexate : evaluation of clinical efficacy and toxicity in T-cell lymphoma. Expert Opin Pharmacother. 2013 Mar;14(4):515-23.
8	Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension.Hepatology. 2016 Jun;63(6):1977-86. doi: 10.1002/hep.28499. Epub 2016 Mar 31.